Dataset Information

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

ABSTRACT: Background:DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.

Methods:We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18?years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.

Results:DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P?-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P_enrichment?=?1; childhood P_enrichment?=?2.00?×?10^-4; adolescence P_enrichment?=?2.10?×?10^-7).

Conclusions:There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

SUBMITTER: Vehmeijer FOL

PROVIDER: S-EPMC7687793 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

Vehmeijer Florianne O L FOL Küpers Leanne K LK Sharp Gemma C GC Salas Lucas A LA Lent Samantha S Jima Dereje D DD Tindula Gwen G Reese Sarah S Qi Cancan C Gruzieva Olena O Page Christian C Rezwan Faisal I FI Melton Philip E PE Nohr Ellen E Escaramís Geòrgia G Rzehak Peter P Heiskala Anni A Gong Tong T Tuominen Samuli T ST Gao Lu L Ross Jason P JP Starling Anne P AP Holloway John W JW Yousefi Paul P Aasvang Gunn Marit GM Beilin Lawrence J LJ Bergström Anna A Binder Elisabeth E Chatzi Leda L Corpeleijn Eva E Czamara Darina D Eskenazi Brenda B Ewart Susan S Ferre Natalia N Grote Veit V Gruszfeld Dariusz D Håberg Siri E SE Hoyo Cathrine C Huen Karen K Karlsson Robert R Kull Inger I Langhendries Jean-Paul JP Lepeule Johanna J Magnus Maria C MC Maguire Rachel L RL Molloy Peter L PL Monnereau Claire C Mori Trevor A TA Oken Emily E Räikkönen Katri K Rifas-Shiman Sheryl S Ruiz-Arenas Carlos C Sebert Sylvain S Ullemar Vilhelmina V Verduci Elvira E Vonk Judith M JM Xu Cheng-Jian CJ Yang Ivana V IV Zhang Hongmei H Zhang Weiming W Karmaus Wilfried W Dabelea Dana D Muhlhausler Beverly S BS Breton Carrie V CV Lahti Jari J Almqvist Catarina C Jarvelin Marjo-Riitta MR Koletzko Berthold B Vrijheid Martine M Sørensen Thorkild I A TIA Huang Rae-Chi RC Arshad Syed Hasan SH Nystad Wenche W Melén Erik E Koppelman Gerard H GH London Stephanie J SJ Holland Nina N Bustamante Mariona M Murphy Susan K SK Hivert Marie-France MF Baccarelli Andrea A Relton Caroline L CL Snieder Harold H Jaddoe Vincent W V VWV Felix Janine F JF

Genome medicine 20201125 1

<h4>Background</h4>DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.<h4>Methods</h4>We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in ...[more]

PMID: 33239103

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Project description:Background/objectivesThe relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.Subjects/methodsThe Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing.ResultsFour CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases.ConclusionsOur findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.

Project description:ImportanceBody mass index (BMI) is used to diagnose obesity in adolescents worldwide, despite evidence that weight does not scale with height squared in adolescents. To account for this, health care providers diagnose obesity using BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is accurate in adolescents.ObjectiveTo compare the accuracy of BMI vs other body fat indices of the form body mass divided by heightn in estimating body fat levels in adolescents.Design, setting, and participantsCross-sectional data from the 1999 to 2006 US National Health and Nutrition Examination Survey were analyzed between September 2015 and December 2016.Main outcomes and measuresDual-energy x-ray absorptiometry and anthropometric data were used to determine changes in body fat levels, body proportions, and the scaling relationships among body mass, height, and percent body fat. To assess the merits of each adiposity index, 3 criteria were used: stability with age, accuracy in estimating percent body fat, and accuracy in classifying adolescents as overweight vs normal weight.ResultsParticipants included 2285 non-Hispanic white participants aged 8 to 29 years. Percent body fat varied with both age and height during adolescence, invalidating the standard weight-to-height regression as the way of finding the optimal body fat index. Because the correct regression model (percent body fat is proportional to mass divided by heightn) suggested that percent body fat scales to height with an exponent closer to 3, we therefore focused on the tri-ponderal mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores. For ages 8 to 17 years, TMI yielded greater stability with age and estimated percent body fat better than BMI (R2?=?0.64 vs 0.38 in boys and R2?=?0.72 vs 0.66 in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI, 17.8%-20.0%; P?<?.001) and performed equally as well as updated BMI percentiles derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95% CI, 6.9%-9.1%; P?=?.62).Conclusions and relevanceThe tri-ponderal mass index estimates body fat levels more accurately than BMI in non-Hispanic white adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight more accurately than BMI z scores and equally as well as updated BMI percentiles but is much simpler to use than either because it does not involve complicated percentiles. Taken together, it is worth considering replacing BMI z scores with TMI to estimate body fat levels in adolescents.

Dataset Information

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

Publications

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

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